Official Title: “Study TRX109013, A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Crossover Study to Evaluate the Efficacy of TREXIMA™ (Sumatriptan + Naproxen Sodium) Versus Butalbital-Containing Combination Medications (BCM) for the Acute Treatment of Migraine When Administered During the Moderate-Severe Pain Phase of the Migraine (Study 1 of 2)”

This study is a multicenter, randomized, double-blind, double-dummy, placebo-controlled, crossover, three-attack, outpatient study in which TREXIMA will be compared to a butalbital-containing combination medication (BCM; acetaminophen 325mg, caffeine 40mg, and butalbital 50mg [Fioricet]) for the acute treatment of migraine headaches.

Subjects will be randomized to one of 6 possible treatment sequences (TPB, TBP, BTP, BPT, PTB, PBT). Subjects will treat each of the 3 migraine attacks when pain is moderate to severe. (T = TREXIMA; P = placebo; B = butalbital)

The study will include 4 visits: (1) a Screening visit at study entry, (2) a Drug Screen visit, (3) a Randomization visit, (4) a Final visit. The Final visit occurs either (A) upon withdrawal, or (B), after treatment of 3 migraine attacks, or C) if the study concludes prior to the subject treating 3 attacks.

The primary objective is to evaluate the efficacy of TREXIMA versus BCM for the acute treatment of moderate/severe migraine.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2008

This study is a multicenter, randomized, double-blind, double-dummy, placebo-controlled, crossover, three-attack, outpatient study in which TREXIMA will be compared to a butalbital-containing combination medication (BCM; acetaminophen 325mg, caffeine 40mg, and butalbital 50mg [Fioricet]) for the acute treatment of migraine headaches.

Subjects will be randomized to one of 6 possible treatment sequences (TPB, TBP, BTP, BPT, PTB, PBT). Subjects will treat each of the 3 migraine attacks when pain is moderate to severe. (T = TREXIMA; P = placebo; B = butalbital)

The study will include 4 visits: (1) a Screening visit at study entry, (2) a Drug Screen visit, (3) a Randomization visit, (4) a Final visit. The Final visit occurs either (A) upon withdrawal, or (B), after treatment of 3 migraine attacks, or C) if the study concludes prior to the subject treating 3 attacks.

The primary objective is to evaluate the efficacy of TREXIMA versus BCM for the acute treatment of moderate/severe migraine.

Intervention(s) in this Clinical Trial

• Drug: Trexima
  • Sumatriptan + Naproxen Sodium
• Drug: Butalbital-containing Combination Medications (BCM)
  • butalbital-containing combination medication (BCM; acetaminophen 325mg, caffeine 40mg, and butalbital 50mg [Fioricet])
• Drug: butalbital
  • butalbital-containing combination medication (BCM; acetaminophen 325mg, caffeine 40mg, and butalbital 50mg [Fioricet])

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 2

Primary Measures

• Subjects with a sustained pain-free (SPF) response from 2-24 hours in subjects using TREXIMA versus those using BCM
  • Time Frame: 2-24 hours
    Safety Issue?: Yes

Secondary Measures

• Subjects who are pain-free (PF) at 2 hours post-treatment
  • Time Frame: 2-48 hours
    Safety Issue?: Yes
• Effects on cognition of treating with BCM vs TREXIMA (as measured by the Mental Efficiency Workload Test (MEWT), measured at 2, 4, 6, 8, 24, and 48 hours
  • Time Frame: 2-48 hours
    Safety Issue?: Yes
• Subjects who use rescue medi
  • Time Frame: 2-48 hours
    Safety Issue?: Yes

Inclusion Criteria:

• Males and females aged 18 to 65 years. If female, using contraception if sexually active and not breastfeeding. If using oral contraceptives, the subjects should be on a stable regimen of oral contraceptives (> 2 months).
• Subjects must have an active prescription for a butalbital-containing medication (BCM), must be currently using it as their primary treatment of migraine, and must have used the BCM to treat at least one migraine within the past 30 days.
• Subjects must have migraine with or without aura (2004 ICHD-II criteria) and must have had at least 2 attacks per month meeting these criteria in three months prior to screening.
• Subjects must be able to understand how to complete the cognitive assessments and all other questionnaires programmed in an electronic diary (eDiary).
• Subject must be able to read English or Spanish and comprehend protocol requirements
• Subject is willing and able to provide written informed consent.

Exclusion Criteria:

• Subject has >8 migraines or 15 headache days per month in total
• Subject has taken >350mg/day of butalbital and/or other barbiturates on average over the 30 days prior to screening.
• Subject has a history of heart disease, abdominal perforation or surgery, abdominal ulcer in last 6 months, abdominal bleeding in last 12 months, bowel disease, and any bleeding disorder
• Subject has allergy, intolerance, or contraindication to the use of any triptan, NSAID, aspirin, barbituates, or acetaminophen (including all sumatriptan and naproxen preparations), has porphyria or has nasal polyps and asthma.
• Subject is currently taking, or has taken in the previous three months, a migraine prophylactic medication containing methysergide or dihydroergotamine; or is taking a migraine or prophylactic medication that is not stabilized (i.e. change of dose within the past 2 months) for either chronic or intermittent migraine prophylaxis or for a co-morbid condition that is not stabilized.
• Subject has a recent history of regular use of opioids or barbiturates, other than
• Butalbital, for the treatment of their migraine headache and/or other non-migraine pain. Regular use is defined as an average of 4 days per month over the last 6 months
• Subject has participated in an investigational drug trial within the previous four weeks or plans to participate in another study at any time during this study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Pozen

Overall Clinical Trial Officials and Contacts

Deo S Bukeyna, Pharm D Study Chair GlaxoSmithKline  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00599157

Study ID Number: TRX109013

ClinicalTrials.gov Identifier: NCT00599157

Health Authority: United States: Food and Drug Administration